Biopolymer Composition for Encapsulating Cells, Method for Producing a Biopolymer Composition for Encapsulating Cells, Method for Promoting Cell Cytoprotection and Use of a Biopolymer Composition for Encapsulating Cells

Abstract

The present invention relates to a biopolymer composition for encapsulating cells, containing alginate, at least one glycosaminoglycan compound, preferably chondroitin sulfate, and at least one component of the extracellular matrix, preferably laminin, and to the process for producing the biopolymer composition. Also disclosed are a method for promoting cytoprotection using this composition, and the use of this composition for preparing a medicament useful in cell transplantation.

Description

FIELD OF THE INVENTION [0001]The present invention is in the field of biotechnology and concerns a biopolymer composition for encapsulation of cells, their preparation process, a method to promote cytoprotection and the use of a biopolymer composition for the preparation of a medicament useful in transplantation cells.BACKGROUND OF THE INVENTION [0002]The search for immunoprotection of transplanted cells (cytoprotection) began in 1964, when the idea of involving cells with ultrathin membranes of polymers was proposed, which has introduced the terms “artificial cells” and “bioencapsulation” in the scientific literature (Chang T M. 1964. semipermeable microcapsules. Science 146:524-525). The bioencapsulation consists of an immunoprotective barrier for cells and methodological principle aims coat cells and / or cell clusters with an artificial membrane, semipermeable, which preserves morphological and functional integrity (Calafiore R., Basta G. 1995. Microencapsulation of pancreatic isl...

AI Technical Summary

Benefits of technology

The present invention is about a biopolymer composition for encapsulation of cells, a process for preparing the composition, a method for promoting cytoprotection, and the use of the composition for transplantation purposes. The invention aims to provide a stable and protective barrier for cells while allowing for the transport of nutrients and oxygen, while preventing bacteria and lymphocytes from causing rejection of the implant. The invention also discusses the use of alginate as a material for the encapsulation of cells, as it has been found to be more suitable than other materials due to its ability to protect cell function and its stability in animals and humans.

Problems solved by technology

The encapsulation process must keep cells viable and protected within a membrane permeable to nutrients, ions, oxygen and other compounds necessary for the maintenance of metabolic functions, but impermeable to bacteria, lymphocytes and the macromolecules responsible for immune and inflammatory reactions, which result in rejection of the implant.

Meanwhile, the use of organic solvents, necessary for solubilizing, greatly interferes in the cell function (Vos P, Hamel A F, Tatarkiewicz K.

The hydrophilicity allows the surface tension between the fluid and adjacent tissue is minimal, reducing protein adsorption and cell adhesion to the biomaterial, which is undesirable for microencapsulation to restrict the diffusion of oxygen and nutrients.

However, recent studies have shown that the presence of these polycations results in an activation of the immune system of the individual receiving the implant, resulting in the loss of function of transplanted microencapsulated cells.

The process for stabilizing the capsule comprises a series of steps, involving little more time in physiological solutions, as well as changes in temperature and CO2 pressure, which may lead to a loss of viability of the cells, which are quite sensitive to these changes.

However, recent studies have shown that the use of polycations for closing pores and consequent acquisition of immunoprotection causes an undesired immune reaction around the microcapsules, jeopardizing the viability and functionality of the implant.

Although there is the state of the art reporting of large number of biopolymer compositions to confer immune protection to certain encapsulated cells, the challenge remains to keep them viable, functional and durable longevity.

This challenge is the result of a number of deleterious conditions to which the cells are subjected during the encapsulation process.

Main disadvantages of the current state of the art are the high susceptibility of encapsulated cells apoptosis and cellular stress due to the conditions provided by the biomaterial coating.

Although the use of polycations such as poly-L-lysine microcapsule results in a narrowing of the pore, it has been shown that is not possible to coat these polycations with alginate and that the inevitable exposure of these molecules on the surface of the microcapsules results in deleterious inflammatory cells microencapsulated (de Vos P, Faas M M, Strand B, Calafiore R. Alginate-based microcapsules for immunoisolation of pancreatic islets.

Furthermore, another disadvantage of the prior art, particularly with regard to the encapsulation of cell groups, such as pancreatic islets, relates to reduced insulin secretion and synthesis, mainly due to the mechanisms of apoptosis and cellular stress, as well as using a large number of cells of pancreatic islets viable for making microcapsules to a pancreatic islet transplantation in patients diagnosed with diabetes.

Finally, it also detects problem as the slowness of conventional microcapsules to achieve normoglycemia after transplantation of pancreatic islet cells microencapsulated in a patient diagnosed with Diabetes.

Images